title: The CIK cells stimulated with combination of IL-2 and IL-15 provide an improved cytotoxic capacity against human lung adenocarcinoma.
abstract: Generation of cytokine-induced killer (CIK) cells is an emerging approach in adoptive donor lymphocyte infusion for patients with a wide range of tumors. However, our previous in vitro studies have shown that the killing efficacy of CIK cells against lung cancer was lower than other tumor cells, while the underlying mechanisms are not clear. We explored the feasibility to improve CIK cells mediated cytotoxicity against lung cancer. Interleukin (IL)-15 is a pleiotropic cytokine that stimulates cytolytic activity and cytokine secretion of NK cells, which may enhance the cytotoxic activity of CIK cells. In this study, we intended to stimulate the CIK cells by IL-2 in combination with IL-15 in cell expansion to achieve enhanced cytotoxicity against lung cancer cells. The different phenotypes of IL-2 or combination of IL-2 and IL-15 stimulated cytokine-induced killer cells were determined, and the improved cytotoxicity of IL-2 and IL-15 induced CIK cells against lung adenocarcinoma were evaluated both in vitro and in vivo. CIK cells stimulated with both IL-2 and IL-15 has shown greater proliferative potential than CIK cells treated with IL-2 alone. IL-15 induction also has driven the expansion of CD3+CD56+ subset and significantly enhanced cytotoxicity against tumor cells. Further analysis has demonstrated that CIKIL-2&IL-15 injected mice models have shown significant tumor regression and lower expression level of CyclinD1 in tumor tissue. This study has provided preclinical evidences that CIKIL-2&IL-15 with enhanced cytotoxicity may offer alternative treatment option for patients with lung cancer.
authors.affiliation: Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunan, People's Republic of China.
authors.forename: Chuanyu
authors.initials: C
authors.lastname: Wei
authors.forename: Wenju
authors.initials: W
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Pang
authors.forename: Mingyao
authors.initials: M
authors.lastname: Meng
authors.forename: Lihong
authors.initials: L
authors.lastname: Jiang
authors.forename: Sha
authors.initials: S
authors.lastname: Xue
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Xie
authors.forename: Ruhong
authors.initials: R
authors.lastname: Li
authors.forename: Zongliu
authors.initials: Z
authors.lastname: Hou
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000628:therapy; D000077192:Adenocarcinoma of Lung; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018929:Cell Culture Techniques / Q000379:methods; D055612:Cytokine-Induced Killer Cells / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016219:Immunotherapy, Adoptive / Q000379:methods*; D019409:Interleukin-15 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D023041:Xenograft Model Antitumor Assays
chemical_list: C569274:IL15 protein, human; D019409:Interleukin-15; D007376:Interleukin-2